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Sex-specific Behavioral Characteristics of Rats with Fetal Valproate Syndrome

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Abstract

Both male and female Wistar rats with an experimental model of autism spectrum disorders induced by prenatal administration of valproate sodium at a dose of 500 mg/kg have behavioral abnormalities similar to people with these disorders, including the abnormalities of social interaction; locomotor, orientation, and exploratory behavior; coordination of movement; spatial exploration behavior; and hyperactivity in previously explored “familiar” environments. The severity of behavioral abnormalities in rats with fetal valproate syndrome exhibits sex differences, which must be taken into account when conducting experimental studies in this model.

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REFERENCES

  1. Lai, M.-C., Lombardo, M.V., Pasco, G., Ruigrok, A.N.V., Wheelwright, S.J., Sadek, S.A., Chakrabarti, B., MRC AIMS Consortium, and Baron-Cohen, S., A behavioral comparison of male and female adults with high functioning autism spectrum conditions, PLoS ONE, 2011, vol. 6, no. 6.

  2. Baron-Cohen, S., Lombardo, M.V., Auyeung, B., Ashwin, E., Chakrabarti, B., and Knickmeyer, R., Why are autism spectrum conditions more prevalent in males?, PLoS Biol., 2011, vol. 9, no. 6.

  3. Lai, M.-C., Lombardo, M.V., Auyeung, B., Chakrabarti, B., and Baron-Cohen, S., Sex/gender differences and autism: Setting the scene for future research, J. Am. Acad. Child Adolesc. Psychiatry, 2015, vol. 54, no. 1, pp. 11–24.

    Article  Google Scholar 

  4. Wilson, C.E., Murphy, C.M., McAlonan, G., et al., Does sex influence the diagnostic evaluation of autism spectrum disorder in adults?, Autism, 2016, vol. 20, no. 7, pp. 808–819.

    Article  Google Scholar 

  5. Hiller, R.M., Young, R.L., and Weber, N.J., Sex differences in autism spectrum disorder based on DSM-5 criteria: Evidence from clinician and teacher reporting, Abnorm. Child Psychol., 2014, vol. 42, no. 8, pp. 1381–1393.

    Article  Google Scholar 

  6. Jeon, S.J., Gonzales, E.L., Mabunga, D.F.N., Valencia, S.T., Kim, D.G., Kim, Y., Adil, K.J.L., Shin, D., Park, D., and Shin, C.Y., Sex-specific behavioral features of rodent models of autism spectrum disorder, Exp. Neurobiol., 2018, vol. 27, no. 5, pp. 321–343.

    Article  Google Scholar 

  7. Mabunga, D.F., Gonzales, E.L., Kim, J.W., Kim, K.C., and Shin, C.Y., Exploring the validity of valproic acid animal model of autism, Exp. Neurobiol., 2015, vol. 24, no. 4, pp. 285–300.

    Article  Google Scholar 

  8. Christensen, J., Gronborg, T.K., Sorensen, M.J., Schendel, D., Parner, E.T., Pedersen, L.H., and Vestergaard, M., Prenatal valproate exposure and risk of autism spectrum disorders and childhood autism, J. Am. Med. Assoc., 2013, vol. 309, no. 16, pp. 1696–1703.

    Article  CAS  Google Scholar 

  9. Rasalam, A.D., Hailey, H., Williams, J.H., Moore, S.J., Turnpenny, P.D., Lloyd, D.J., and Dean, J.C., Characteristics of fetal anticonvulsant syndrome associated autistic disorder, Dev. Med. Child Neurol., 2005, vol. 47, no. 8, pp. 551–555.

    Article  CAS  Google Scholar 

  10. Kim, K.C., Kim, P., Go, H.S., Choi, C.S., Park, J.H., Kim, H.J., Jeon, S.J., Dela, PenaI.C., Han, S.H., Cheong, J.H., Ryu, J.H., and Shin, C.Y., Male-specific alteration in excitatory post-synaptic development and social interaction in pre-natal valproic acid exposure model of autism spectrum disorder, J. Neurochem., 2013, vol. 124, no. 6, pp. 832–843.

    Article  CAS  Google Scholar 

  11. Cho, H., Kim, C.H., Knight, E.Q., Oh, H.W., Park, B., Kim, D.G., and Park, H.-J., Changes in brain metabolic connectivity underlie autistic-like social deficits in a rat model of autism spectrum disorder, Sci. Rep., 2017, vol. 7, no. 1.

  12. Schneider, T., Roman, A., Basta-Kaim, A., Kubera, M., Budziszewska, B., Schneider, K., and Przewłocki, R., Gender-specific behavioral and immunological alterations in an animal model of autism induced by prenatal exposure to valproic acid, Psychoneuroendocrinology, 2008, vol. 33, no. 6, pp. 728–740.

    Article  CAS  Google Scholar 

  13. Kataoka, S., Takuma, K., Hara, Y., Maeda, Y., Ago, Y., and Matsuda, T., Autism-like behaviours with transient histone hyperacetylation in mice treated prenatally with valproic acid, Int. J. Neuropsychopharmacol., 2013, vol. 16, no. 1, pp. 91–103.

    Article  CAS  Google Scholar 

  14. Anshu, K., Nair, A.K., Kumaresan, U.D., Kutty, B.M., Srinath, S., and Laxmi, T.R., Altered attentional processing in male and female rats in a prenatal valproic acid exposure model of autism spectrum disorder, Autism Res., 2017, vol. 10, no. 12, pp. 1929–1944.

    PubMed  Google Scholar 

  15. Bambini-Junior, V., Rodrigues, L., Behr, G.A., Moreira, J.C.F., Riesgo, R., and Gottfried, C., Animal model of autism induced by prenatal exposure to valproate: Behavioral changes and liver parameters, Brain Res., 2011, vol. 1408, pp. 8–16.

    Article  CAS  Google Scholar 

  16. Lin, H.C., Gean, P.W., Wang, C.C., Chan, Y.H., and Chen, P.S., The amygdala excitatory/inhibitory balance in a valproate-induced rat autism model, PLoS ONE, 2013, vol. 8, no. 1.

  17. Vataeva, L.A., Age-related changes in the level of anxiety in male and female rats in the test of an elevated cruciform labyrinth, Zh. Evol. Biokhim. Fiziol., 2003, vol. 39, no. 4, pp. 379–383.

    CAS  PubMed  Google Scholar 

  18. Shishelova, A.Yu., The formation of sex differences in the development of research activity in rats of the puberty period, Zh. Vyssh. Nervn. Deyat., 2012, vol. 62, no. 1, pp. 33–42.

    Google Scholar 

  19. Kerr, D.M., Downey, L., Conboy, M., Finn, D.P., and Roche, M., Alterations in the endocannabinoid system in the rat valproic acid model of autism, Behav. Brain Res., 2013, vol. 249, pp. 124–132.

    Article  CAS  Google Scholar 

  20. Rukovodstvo po provedeniyu doklinicheskikh issledovanii lekarstvennykh sredstv (Guidelines for Preclinical Studies of Drugs), Mironov, A.N., Ed., Moscow: Grif i K, 2012, part 1.

  21. Vallée, M., Mayo, W., Dellu, F., Le Moal, M., Simon, H., and Maccari, S., Prenatal stress induces high anxiety and postnatal handling induces low anxiety in adult offspring: Correlation with stress-induced corticosterone secretion, J. Neurosci., 1997, vol. 17, no. 7, pp. 2626–2636.

    Article  Google Scholar 

  22. Kaidanovich-Beilin, O., Lipina, T., Vukobradovic, I., Roder, J., and Woodgett, J.R., Assessment of social interaction behaviors, J. Visualized Exp., 2011, no. 48.

  23. Silverman, J.L., Yang, M., Lord, C., and Crawley, J.N., Behavioral phenotyping assay for mouse models of autism, Nat. Rev. Neurosci., 2010, vol. 11, no. 7, pp. 490–502.

    Article  CAS  Google Scholar 

  24. Iwata, K., Izumo, N., Matsuzaki, H., et al., Vldlr overexpression causes hyperactivity in rats, Mol. Autism, 2012, vol. 3, no. 1.

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Funding

The work was performed within the scope of State Assignment no. 0521-2019-0007.

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Authors and Affiliations

  1. Laboratory of Psychopharmacology, Zakusov Institute of Pharmacology, 125315, Moscow, Russia

    I. G. Kapitsa, E. A. Ivanova & T. A. Voronina

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  1. I. G. Kapitsa
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  2. E. A. Ivanova
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  3. T. A. Voronina
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Correspondence to I. G. Kapitsa.

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Conflict of interest. The authors declare that they have no conflict of interest.

Statement on the welfare of animals. All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

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Translated by E.V. Makeeva

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Kapitsa, I.G., Ivanova, E.A. & Voronina, T.A. Sex-specific Behavioral Characteristics of Rats with Fetal Valproate Syndrome. Moscow Univ. Biol.Sci. Bull. 75, 89–95 (2020). https://doi.org/10.3103/S0096392520020054

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  • DOI: https://doi.org/10.3103/S0096392520020054

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